Molecular dynamics simulation of PNPLA3 I148M polymorphism reveals reduced substrate access to the catalytic cavity
文献类型：期刊论文
| 作者 | Xin YN1,2; Zhao YQ3; Lin ZH2; Jiang XJ2; Xuan SY[*]1,2; Huang JF[*]3,4 |
| 刊名 | PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
 |
| 出版日期 | 2013 |
| 卷号 | 81期号:3页码:406-414 |
| 关键词 | PNPLA3 nonalcoholic fatty liver disease missense mutation molecular dynamics simulations |
| 通讯作者 | dxyxyn@163.com ; huangjf@mail.kiz.ac.cn |
| 合作状况 | 其它 |
| 英文摘要 | A missense mutation I148M in PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is significantly correlated with nonalcoholic fatty liver disease (NAFLD). To glean insights into mutation's effect on enzymatic activity, we performed molecular dynamics simulation and flexible docking studies. Our data show that the size of the substrate-access entry site is significantly reduced in mutants, which limits the access of palmitic acid to the catalytic dyad. Besides, the binding free energy calculations suggest low affinity for substrate to mutant enzyme. The substrate-bound system simulations reveal that the spatial arrangement of palmitic acid is distinct in wild-type from that in mutant. The substrate recognition specificity is lost due to the loop where the I148M mutation was located. Our results provide strong evidence for the mechanism by which I148M affects the enzyme activity and suggest that mediating the dynamics may offer a potential avenue for NAFLD. |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China; Grant numbers: 31123005, 81170337; Grant sponsor: Chinese Academy of Sciences; Grant number: Y002731071; Grant sponsor: Shandong Provincial Natural Science Foundation, China; Grant number: ZR2009CM015; Grant sponsor: National Basic Research Program of China; Grant number: 2009CB941300. |
| 语种 | 英语 |
| WOS记录号 | WOS:000314179600005 |
| 公开日期 | 2013-03-04 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7220]  |
| 专题 | 昆明动物研究所_结构生物信息学 昆明动物研究所_遗传资源与进化国家重点实验室 |
| 作者单位 | 1.College of Medicine and Pharmaceutics, Ocean University of China, Qingdao 266003, Shandong Province, China 2.Qingdao Municipal Hospital, Qingdao 266021, Shandong Province, China 3.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 4.Kunming Institute of Zoology-Chinese University of Hongkong Joint Research Center for Bio-resources and Human Disease Mechanisms, Kunming 650223, China |
| 推荐引用方式 GB/T 7714 | Xin YN,Zhao YQ,Lin ZH,et al. Molecular dynamics simulation of PNPLA3 I148M polymorphism reveals reduced substrate access to the catalytic cavity[J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,2013,81(3):406-414. |
| APA | Xin YN,Zhao YQ,Lin ZH,Jiang XJ,Xuan SY[*],&Huang JF[*].(2013).Molecular dynamics simulation of PNPLA3 I148M polymorphism reveals reduced substrate access to the catalytic cavity.PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,81(3),406-414. |
| MLA | Xin YN,et al."Molecular dynamics simulation of PNPLA3 I148M polymorphism reveals reduced substrate access to the catalytic cavity".PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 81.3(2013):406-414. |
入库方式： OAI收割
来源：昆明动物研究所
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